Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

SBL Test 1 > Review: Myeloid Disorders > Flashcards

Review: Myeloid Disorders Flashcards

1
Q

What is the pathogenesis of problems caused by Acute Leukemias?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

In Acute Leukemias/lymphomas, a proliferation of -blasts causes what?

A

Suppression of NL hematopoeisis

    1. Anemia
  • 2. Thrombocytopenia
  • 3. Neutropenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are differences seen in ALL and AML?

A
  1. ALL
    1. Lymphoblasts (TdT+)
    2. Children
    3. T-ALL = teenager and thymic mass
  2. AML
    1. Myeloblasts (MPO+ and auer rods)
    2. Older people >60
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Myeloblasts are positive for what marker?

A

MPO (=> auer rods)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Markers for AML

A
  1. CD33+
  2. CD34+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Acute Myeloid Leukemia (AML)

A

Malignant proliferation of myeloblasts in the BM.

  1. Released into bloodstream = leukocytosis
  2. Fill up BM => supress of NL hematopoeisis (pancytopenia)
    1. Anemia,
    2. Thrombocytopenia
    3. Neutropenia
  3. M5 = gum infiltation (gingival hyperplasia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In order to qualify as AML, on biopsy of the BM what must we see?

A

at least 20% of BM is myeloblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

AML is MC in who?

A
  • >60 YO Males
  • If in younger adults: balanced translocations
    1. t(8:21)
    2. inv(16)
    3. t(15:17)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Most genetic abnormalities in AML..

A
  1. Most genetic abnormalities in AML interfere with TF that are required for NL myeloid cell to differentiate.
  2. Karyotypic aberrations are found in 90% of cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Most common chromosomal rearrangements in AML

A
  1. t(8:21): disrupt RUNX1 gene (M2) ***
  2. inv(16): disrupt CBFB gene (M4) **
  3. t(15;17): PML- RAR-a fusion gene (Acute Promyelocytic Leukemia/M3); + FLT3 activating mutation
  4. t(11q23;v): involve MLL (M4/5)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

RF for AML

A
  1. Alkylating chemotherapy
  2. Radiation
  3. MPD
  4. Down Syndrome (Also RF in ALL)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Clinical Presentation of Acute Myeloid Leukemia

A

Present with similar clinical picture as ALL: sx of pancytopemia

  1. Anemia = >Fatigue (anemia)
  2. Neutropenia => fever/ Opportunistic infections (fungi, pseudomonas, commensals and pneumocystis) of oral cavity, skin GI/GU tract.
  3. Thrombocytopenia => spontaneous mucosal and cutaneous bleeding (worse in APML)
    1. Petechiae, ecchymoses, mucosal hemorrhages and hematuria

M5 = AML with monocytic differentiation = gingival swelling and skin infiltration (leukemia cytis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are differences in clinical presentation of ALL and AML?

A

AML is LESS likely to present with (but still CAN)

  1. Bone pain
  2. LAD
  3. Hepatosplenomegaly
  4. CNS/testes spread
  5. Rarely presents as a mass
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Diagnosis of Acute Myeloid Leukemia

A
  1. Myeloid specific antigen stains (MPO and non-specific esterases)
  2. BM exam is REQUIRED = >20% of myeloblasts in BM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

WHO Classification of AML: Class 1, 2 and 3

What is Class I AML?

Prognosis?

A

AML + genetic aberrations

Favorable prognosis:

  1. t(8:21),
  2. inv(16)

Intermediate prognosis:

  1. t(15;17)

Poor prognosis:

  1. t(11;q23:v)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

WHO Classification of AML: Class 1, 2 and 3

What is Class 2 AML?

Prognosis?

A

AML with MDS-like features

All have poor prognosis

  1. AML due to prior MDS
  2. MDS-like cytogenic aberrations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

WHO Classification of AML: Class 1, 2 and 3

What is Class 3 AML?

Prognosis?

A

AML that is therapy related

All VERY POOR prognosis

  1. AML due to alkylating chemo/radiation
  2. Post- topoisomerase-II inhibitrs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the FAB Classification of AML?

  • M0 =
  • M1 =
  • M2=
  • M3 =
  • M4 =
  • M5a/b =
  • M6a/b =
  • M7 =
A
  • M0 = Minimally differentiated AML
  • M1 = AML without maturation
  • M2= AML with myelocytic maturation
  • M3 = Acute Promyelocytic Leukemia
  • M4 = Acute myelomonocytic Leukemia (with myelomonocytic maturation)= AMML
  • M5a/b = Acute Monocytic Leukemia (with monocytic maturation)
  • M6a/b = Acute Erythroleukemia (with erythroid maturation)
  • M7 = Acute Megakaryotic Leukemia (with megakaryocytic maturation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Name this classifcation of AML:

Blasts lack cytologic and cytochemical markers of myeloblasts

A

M0 - AML, minimally differentiated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What do you see in

M1: AML without maturation

A

20% of cases

Very immature cells

  1. >3% are MPO(+)
  2. Few granules or Auer rods
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do you see in

M2: AML with myelocytic maturation

A
  • t(8:21) = MC type (30-40%)
  • All granulocytes have undergone myeloid maturation
  • Auer rods are present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do you see in

M3: Acute Promyelocytic Leukemia

A
  • Pts are younger (35-40 yo)
  • Most cells are hypergranular promyelocytes
  • t(15:17) with FLT3 activating mutation => PML-RARA fusion gene
    • Chr 15 = Retinoic acid receptor- alpha (RARA) is dysfunctional: prevents NL maturation of promyelocytes => INC amounts of promyelocytes, which contains MANY Auer rods => if they leak out of cell => INC risk of DIC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the treatment for Acute Promyelocytic Leukemia?

A

All trans-retinoid acid (form of Vitamin A): ABNL cells will mature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What do you see in

M4: with myelomonocytic maturation (Acute myelomonocytic Leukemia/ AMML)

A
  1. Inv(16)
  2. Cells = Myelocytic and monocytic differention
  3. Myeloid cells = MPO +
  4. Monoblasts = Non-specific esterase (+), no auer rods and MPO (-)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What do you see in ## Footnote **M5 a/b = Acute monocytic Leukemia**
**O O O** 1. ONLY monoblasts (MPO-, non-specific esterase +) 2. Older patients 3. Organomegaly, LAD and tissue infiltration 1. Swollen gums 2. Fungal skin infections 3. Leukemia cutis 4. Orbital Granuloctic sarcoma
26
If **AML** occurs in **younger patients,** what translocations do we see?
1. **t(8:21) = disrupt RUNX1 gene** 2. **inv (16) =\> disrupt CBFB gene** 3. **t(15:17)**
27
What is prognosis of AML?
Depends on pathogenesis: * Overall, **60%** achieve complete remission with chemotherapy; relapse is common. **t(5:17)** = cured with all trans retinoic acid and arsenic salts
28
What are **Myeloproliferative Disorders?**
Mutation of a multipotent progenitor cells (Common myeloid progenitor) in the **BONE MARROW** results in a **constitutively activated TK** =\> 1. P**ancytosis** (high WBC, RBC and platelets) 2. **hypercellular marrow**, **BUT; 1 cell line is affected the MOST.** * Does NOT impair differentiation
29
**Myeloproliferative disorders** are MC in who?
**Older adults**
30
**Myeloproliferative Disorders (4)**
1. **Chronic Myeloid Leukemia:** lots of granulocytes 2. **Polycythemia Vera:** lots of RBC 3. **Essential thrombocytosis: l**ots of platelets 4. **Primary Myelofibrosis:**
31
What are common clinical features of **Myeloproliferative Disorders?**
Suppression of NL hematopoiesis: Neoplastic cells and products displace NL BM : tend to have thrombocytosis (?) Extramedullary hematopoiesis: HSCs home at non-marrow sites Bleeding: paradoxically occurs because the platelets are functionally ABNL Transform into spent phase (marrow fibrosis + cytopenia) OR AML (or ALL, which has an even worse prognosis than becoming AML)
32
In **Myeloproliferative Disorders,** what cells are increased?
Cells of **ALL myeloid lineages (WBC, RBC and platelets)**
33
Common complications in **Myeloproliferative Disorders**
1. Increased cell turnover =\> increase risk for **hyperuricemia** and **gout** 2. **Extramedullary hematopoeisis** 3. **Bleeding** 4. Can progress to **marrow fibrosis (spent phase)** 5. Can transform to **acute leukemia** (AML is MC, but ALL can occur to and if so, worse prognosis
34
What is **Chronic Myelogenous Leukemia (CML)?**
Mutation in **HSC** that causes proliferation of **mature myeloid granulocytes** (_neutrophils_ and _ESPECIALLY basophils_)
35
\***Basophilia** is HIGHLY associated with \_\_\_\_
CML
36
**Chronic Myelogenous Leukemia** is due to what genetic abnormality?
**t(9:22) Philadelphia Chr =\>** **BCR-ABL fusion gene** =\> constitutive activation of ABL TK
37
1st line treatment for **CML**
**Imatinib** (blocks TK activity)
38
Clinical presentation of **Chronic Myelogenous Leukemia**
1. Insidious onset of fatigue (anemia), WL, anorexia, + 2. **LUQ “dragging” abdominal pain** due to _splenomegaly_ (_extramedullary hematopoiesis_, expanded red pulp) that often contains infarcts of varying age 3. Potential hepatosplenomegaly and lymphadenopathy
39
How do we diagnose **Chronic Myeloid Leukemia?**
1. **Leukocytosis** (**\>100,000**mm3, with immature forms \< 10% blasts) 2. **Hypercellular BM:** ↑ maturing granulocyte precursors =\> ↑ eosinophils, basophils and megakaryocytes 1. Sea-blue histiocytes 2. INC reticulin 3. **t(9:22) BCR-ABL fusion gene** 4. **Low LAP**: helps to differentiate infection vs cancer.
40
How do we differentiate **Chronic Myeloid Leukemia** from **Leukmoid Reaction?**
1. CML granulocytes are LAP (-) 2. Increased basophils 3. T(9:22)
41
What is a complication of **CML**?
Transformation into **AML** or **ALL** (can transform to either bc mutation is in HSC).
42
What is **Polycythemia Vera?**
Neoplastic proliferation of mature myeloid cells in BM, especially **RBC**.
43
What findings on CBC will a patient with **Polycythemia Vera have?**
1. **Leukocytosis** (12,000-50,000) 2. **Thrombocytosis** (\>500,000) 3. **Erythrocytosis** (higher relative to others, causing symptoms): ↑RBC mass. ↑ Hb, ↑ Hct = \>60%
44
What is the genetic abnormality we see in **Polycythemia Vera?**
**JAK2 point mutation:** constitutive activation of JAK2 kinase (Valine = Phenylalanine at residue 617) * 1. (+) of JAK2 kinase * 2. Stimulates erythropoietin and thrombopoietin RECEPTORS * 3. ↑ production of RBC (RBC mass); ↑Hgb, Hct and RBC count * 4. Thus, due to negative FB, ↓ EPO.
45
In **PV**, what are O2 and EPO levels?
* **O2 = NL** * **EPO = low**
46
To differentiate PV from other causes ↑ RBC mass/ Reactive polycythemia: **_Reactive polycythemia due to lung disease (hypoxia)_**
Reactive polycythemia due to lung disease: * PaO2 = ↓ * EPO = high PV: * paO2= NL * EPO is ↓.
47
To differentiate PV from other causes ↑ RBC mass/ Reactive polycythemia: **_Reactive polycythemia due to ectopic EPO production (RenalCC):_**
**Reactive polycythemia** due to ectopic EPO production (RenalCC): * SaO2 = NL; * EPO = high **PV:** * paO2= NL * EPO is ↓
48
Clinical Presentation of **Polycythemic Vera** What are the symptoms due to =\>
**_Insidious onset, usually adults of late-middle age._** Symptoms due to ↑ RBC mass (Erythrocytosis) 1. **Thrombosis** (DVT, MI, stroke): often 1st symptom 1. **Budd-Chiari syndrom**e (thrombosis in hepatic vein =\> liver infarcts) 2. **Erythrocytosis:** 1. Plethoric (too much blood in body) 2. Cyanotic: HA/dizziness and HTN 3. Hyperviscosity symptoms: blurry vision, HA. 3. **Basophilia** = hot showers trigger histamine release =\> itching after warm bath or shower and peptic ulcers 4. **High cell turnover** =\> hyperuricemia and symptoms of gout. 5. Late in disease: **organomegaly** High cell turnover è hyperuricemia and symptoms of gout. Late in disease: organomegaly
49
Prognosis and treatment of PV
1. **Without treatment** = death from bleeding or thrombosis within months. 2. **Plebotomy** extends median survival to about 10 years
50
Complications of PV
1. **Budd-Chiari** 2. **Hyperuricemia** and **gout** 3. **Organomegaly** 4. **Extensive marrow fibrosis** can displace HSC =\> **extramedullary hematopoeisis**
51
J**AK2 point mutation,** which causes it to be active all the time, is occurs in what Myeloproliferative disorders?
1. **PV** 2. **Essential Thrombocytosis** 3. **Primary Myelofibrosis**
52
What is **Essential Thrombocytosis?**
Neoplastic proliferation of mature myeloid cells in BM, especially **platelets**. (megakaryocytes are INC in #/size). + 1. Leukocytosis/granulocytes 2. Erythrocytosis
53
Mutations that cause **Essential Thrombocytosis**
1. 50-60% = **JAK2 point mutation:** constitutive activation of JAK2 kinase (Valine = Phenylalanine at residue 617) 2. 5-10% = **MPL point mutation** = constitutive activates MPL kinase
54
What will TPO levels be in **Essential Thrombocytosis?**
↓ TPO.
55
Clinical presentation of **Essential Thrombocytosis**
Symptoms due to ABNL platelets: **↑ risk of bleeding OR thrombosis** * 1. Thrombosis (DVT, MI, stroke and portal/hepatic V. thrombosis) * 2. Hemorrhage * 3. Mild organomegaly * 4. Erythromelagia, throbbing and burning of hands and feet
56
How are Essential Thrombocytosis different from other Myeloproliferative Disorders?
1. \***RARELY** progresses to marrow fibrosis/acute leukemia/ 2. \***NO** significant risk for hyperuricemia or gout
57
BM in **Essential Thrombocytosis**
1. Mild Hypercellular 2. ↑ megakaryocytes 3. ABNL, many large platelets, with counts \>1,000,000/mL 4. Mild leukocytosis
58
What is **Primary Myelofibrosis?**
Neoplastic proliferation of mature myeloid cells in BM, especially **megakaryocytes**.
59
In Primary Myelofibrosis, how do INC in megakaryocytes cause problems?
1. Releases **PDGF** & **TGF-B** 2. =\> causes e**xcess collagen production** from N**ON-neoplastic fibroblasts** 3. =\> **obliterative marrow fibrosis** and **scarring**
60
Clinical Presentation of **Primary Myelofibrosis**
_Medullary fibrosis_ causes 1. **Progressive anemia (**normochromic, normocytic) =\> fatigue 2. **LUQ fullness** due to marked **splenomegaly** due to **extramedullary hemotopoeisis** -sometimes only finding (like CML) 3. **Cytopenias** 4. **Leukoerythroblastosis**: Fibrosed marrow causes premature release of _NUCLEATED_ erythroid and early granulocyte progenitors 5. Increased risk of infection, thrombosis and bleeding =\> death
61
What histology finding do you see in **Primary Myelofibrosis?**
**Teardrop-shaped red cells:** tear-drop shaped RBC damaged by during release from fibrotic marrow

SBL Test 1 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions